Raised tone reveals ATP as a sympathetic neurotransmitter in the porcine mesenteric arterial bed

Abstract

The relative importance of ATP as a functional sympathetic neurotransmitter in blood vessels has been shown to be increased when the level of preexisting vascular tone or pressure is increased, in studies carried out in rat mesenteric arteries. The aim of the present study was to determine whether tone influences the involvement of ATP as a sympathetic cotransmitter with noradrenaline in another species. We used the porcine perfused mesenteric arterial bed and porcine mesenteric large, medium and small arteries mounted for isometric tension recording, because purinergic cotransmission can vary depending on the size of the blood vessel. In the perfused mesenteric bed at basal tone, sympathetic neurogenic vasocontractile responses were abolished by prazosin, an α 1 -adrenoceptor antagonist, but there was no significant effect of α,β-methylene ATP, a P2X receptor-desensitizing agent. Submaximal precontraction of the mesenteric arterial bed with U46619, a thromboxane A 2 mimetic, augmented the sympathetic neurogenic vasocontractile responses; under these conditions, both α,β-methylene ATP and prazosin attenuated the neurogenic responses. In the mesenteric large, medium and small arteries, prazosin attenuated the sympathetic neurogenic contractile responses under conditions of both basal and U46619-raised tone. α,β-Methylene ATP was effective in all of these arteries only under conditions of U46619-induced tone, causing a similar inhibition in all arteries, but had no significant effect on sympathetic neurogenic contractions at basal tone. These data show that ATP is a cotransmitter with noradrenaline in porcine mesenteric arteries; the purinergic component was revealed under conditions of partial precontraction, which is more relevant to physiological conditions.

Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations

“…Sympathetic vasomotor reflexes have been described as involving simultaneous NA and ATP release, both acting on vascular smooth muscle cells 56 57 58 . The importance of ATP as a functional sympathetic neurotransmitter in blood vessels depends on the species, the vascular bed, the type of blood vessel and the pathology analysed 59 . In this sense, changes in purinergic cardiovascular signalling have been described in liver pathologies 60 61 .…”

Purinergic control of lysenin’s transport and voltage-gating properties

“…Neurotransmission, secretion, transduction, cell proliferation, motility, and differentiation are typical examples of biological functions modulated by nucleotides or nucleosides acting as extracellular signaling molecules [5][6][7][8][9][10][11]. Burnstock's early hypothesis that ATP, the major intracellular molecule providing the energy required for multiple biochemical and biophysical processes, may actually function as an extracellular non-adrenergic and noncholinergic signaling molecule [12,13] was received with great skepticism [14,15].…”

Purinergic regulation of the immune system

“…In addition, various mechanisms have evolved to enable the controlled release of ATP, ADP and other nucleotides from intact cells. These include the release of nucleotides in granules from nerve terminals 8 , platelets 9 and mast cells 10 .…”